1. Field of the Invention
The present invention relates to an artificial blood vessel. In particular, the present invention relates to an artificial blood vessel which is preferably used as a substitute blood vessel for replacing small-diameter blood vessels such as coronary arteries, peripheral blood vessels and the like.
2. Description of the Related Art
Tubes of woven or knitted fabric of polyester fibers and expanded polytetrafluoroethylene (hereinafter referred to as "EPTFE") are used as artificial blood vessels. The EPTFE tubes are practically used in a smaller diameter range rather than the polyester tubes since PTFE itself has excellent anti-thrombotic properties, and the pore structure of EPTFE tube comprising fibrils and nodes which is obtained by expanding PTFE tube has excellent biocompatibility.
However, EPTFE does not always have satisfactory anti-thrombotic properties, and the EPTFE tubes do not have a sufficient patency ratio when they have an inner diameter of 5 mm or less, in particular 4 mm or less. To remove this drawback of the EPTFE tube, the following methods have been proposed:
(1) improvement of anti-thrombotic properties of materials of artificial blood vessels; PA1 (2) growing or seeding anti-thrombotic tissues on inner surfaces of artificial blood vessels; and PA1 (3) accelerating the formation of tissues on inner surfaces of artificial blood vessels after grafting the artificial blood vessels. PA1 a tube formed from expanded polytetrafluoroethylene comprising fibrils and nodes connecting fibrils, in which the inner surface of said tube and the surfaces of pores in a layer portion extending from the inner surface of said tube to a depth of at least 5% in a radial direction from said inner surface are made hydrophilic, and PA1 a tissue-inducing substance which is immobilized on said inner surface and said surfaces of pores which are made hydrophilic.
Concretely, as the method (1), developments of anti-thrombotic polymer materials having a microphase separation structure or anti-thrombotic agent-immobilized materials have been discussed (see Noishiki et al, Trans. A. S. A. I. O., 23, 253 (1977), JP-A-58-180162 and JP-A-63-119773). Such the anti-thrombotic materials can prevent the formation of thrombus temporarily after grafting, but thrombus forms and occludes the blood vessels after a long time from grafting.
As the method (2), a method for seeding vascular endothelial cells on the inner walls of artificial blood vessels has been proposed. However, the provision of human vascular endothelial cells is difficult, and the collection and culturing of such the cells require several weeks. Therefore, this method has not been used in practice (see Takagi et al, JINKOZOKI (Japanese Journal of Artificial Organs), 17, 679 (1988) and JP-A-1-170466).
As the method (3), artificial blood vessels on which endothelial cell-adhesion or growth materials are coated or covalently bonded have been proposed.
An artificial blood vessel is known, which sustainingly releases heparin for imparting anti-thrombotic properties to the blood vessel. For example, an artificial blood vessel to which heparin is immobilized using a material containing a quaternary ammonium salt or protamine has been proposed (see JP-A-58-180162 and JP-A-63-119773).
An artificial blood vessel on which the endothelial cell-adhesion material and optionally the endothelial cell-growth material are coated is proposed, but the formation of endothelial cells is not accelerated and the patency does not improve (C. H. Lundgren et al, Trans. A. S. A. I. O., 32, 346 (1986), and Glysler et al, SURGERY, 112, 244 (1992)).
An artificial blood vessel to which an endothelial cell-adhesion material is chemically immobilized is proposed (see JP-A-5-269198). In addition, an article reports that a material to which the endothelial cell-adhesion material and endothelial cell-growth material are both covalently bonded facilitated the formation of endothelial cells in vivo. However, an artificial blood vessel made of such the material loses its effects after grafting, and its patency is unsatisfactory (see J. Biomed. Mater. Res., 27, 901 (1993), etc.).
Furthermore, an artificial blood vessel which is coated with an endothelial cell-adhesion material such as collagen or gelatin and heparin has been proposed for suppressing the formation of thrombus prior to the formation of endothelial cells. However, neither the formation of endothelial cells nor the suppression of the thrombus formation is insufficient, and no satisfactory patency is achieved (see JP-A-63-46169).
A required amount of heparin must be released in a requisite period after grafting for achieving a high patency ratio. In particular, a required amount and requisite period for releasing heparin vary with the conditions of living bodies such as the blood flow and inner diameters of blood vessels to be replaced. Therefore, it is necessary to design a heparin-immobilized artificial blood vessel which satisfy the releasing amount and period of heparin according to respective artificial blood vessels.
However, it is difficult for the conventional heparin-immobilized artificial blood vessels to control the amount of immobilized heparin and the rate of sustained release of heparin since heparin is ionically bonded to the quaternary ammonium salt or protamine which has been coated on the surface of the artificial blood vessel. Therefore, it is difficult to sustainingly release heparin in a sufficient amount for maintaining the patency of artificial blood vessel in a requisite period, and the sufficient patency ratio is not attained.